(i) Field of the Invention
The present invention relates to a method for the diagnosis of diseases by genetic analysis, in particular the analysis of genes for subunits of the human guanine nucleotide-binding proteins (G proteins).
(ii) Description of the Related Art
Heterotrimeric guanine nucleotide-binding proteins (G proteins) have an outstanding importance in intracellular signal transduction. They mediate the relaying of extracellular signals after stimulation of hormone receptors and other receptors which undergo a conformational change after receptor activation. This leads to activation of G proteins which may subsequently activate or inhibit intracellular effectors (eg. ion channels, enzymes). Heterotrimeric G proteins consist of three subunits, the .alpha., .beta. and .gamma. subunits. To date, several different .alpha. subunits, 5 .beta. subunits and about 12 .gamma. subunits have been detected by biochemical and molecular biological methods (Binbaumer, L. and Bimnbaumer, M. Signal transduction by G proteins: 1994 edition. J.Recept.Res. 15:213-252, 1995; Offermanns, S. and Schultz, G. Complex information processing by the transmembrane signaling system involving G proteins. Naunyn Schmiedebergs Arch.Pharmacol. 350:329-338, 1994; NUrnberg, B., Gudermann, T., and Schultz, G. Receptors and G proteins as primary components of transmembrane signal transduction. Part 2. G proteins: structure and function. J.Mol.Med. 73:123-132, 1995; Neer, E. J. Heterotrimeric G proteins: Organizers of Transmembrane Signals. Cell 80:249-257, 1995;. Rens-Domiano, S. and Hamm, H.E. Structural and functional relationships of heterotrimeric G-proteins. FASEB J. 9:1059-1066, 1995).
Receptor-medi ated activation of certain .alpha. subunits can be inhibited by pretreatment with pertussis toxin (PTX). These include, in particular, the .alpha. isoforms .alpha.i1, .alpha.i2 and .alpha.i3, and various o.alpha. subunits. G proteins of these types are also referred to as PTX-sensitive G proteins.